Teclistamab/Talquetamab Hits Record Low Hazard Ratio in Multiple Myeloma

Topline results from the phase 3 MonumenTAL-6 trial (NCT06208150) showed that teclistamab-cqyv (Tecvayli) plus talquetamab-tgvs (Talvey) reduced the risk of disease progression or death by 89% (HR, 0.11; 95% CI, 0.08-0.16; P <.0001) and the risk of death by 62% (HR, 0.38) compared with investigator’s choice of elotuzumab (Empliciti) plus pomalidomide (Pomalyst) and dexamethasone (EPd) or pomalidomide plus bortezomib (Velcade) and dexamethasone (PVd), in patients with relapsed/refractory multiple myeloma who received 1 to 4 prior lines of therapy.¹ The trial also assessed talquetamab plus pomalidomide, which reduced the risk of progression by 73% (HR, 0.27; 95% CI, 0.2-0.35) compared with investigator’s choice.¹

Ajay K. Nooka, MD, MPH, FACP, professor and director of the Myeloma Program in the Department of Hematology and Medical Oncology at Emory University School of Medicine and associate director for clinical research at Winship Cancer Institute of Emory University, spoke with CancerNetwork® about what this risk reduction means for counseling patients today.

Transcript:

We have 1 GPRC5D bispecific antibody that was approved in the late-relapse setting: talquetamab.² What’s the role of talquetamab in the early-relapse setting? In the late-relapse setting, response rates were 70% to 75%, against an expected response rate of less than 30% in that population. We know it is a very good agent. In one of the earlier trials exploring talquetamab combinations, talquetamab plus pomalidomide showed a lot of correlative data on how the immunomodulatory agents—lenalidomide and pomalidomide—help with immune activation, with an increase in the CD8 T cells and an increase in interferon gamma to kill the myeloma cells. Those were abundantly seen with this combo, which is why that became the second arm [of MonumenTAL-6]. The primary arm uses talquetamab and teclistamab together, targeting both GPRC5D and BCMA. Why did we use that combination? The RedirecTT-1 trial [NCT04586426] had shown that this combination, even in heavily refractory patients, including those with extramedullary disease, achieved a response in close to 80% of patients.³

That is how the 3 arms of MonumenTAL-6 were designed, compared against a control arm of [investigator’s choice of EPd or PVd]. For the experimental arm of teclistamab plus talquetamab, the PFS hazard ratio is 0.11, the best hazard ratio we have ever seen in the history of multiple myeloma. This has also been shown in the secondary end point of overall survival, where the hazard ratio was [0.38], a [62%] reduction in the risk of death in early-relapse myeloma. These are all favoring the usage of talquetamab and teclistamab as a combination.

This is how I counsel my patients: the traditional therapies we use—[daratumumab plus pomalidomide and dexamethasone or daratumumab plus bortezomib (Velcade) and dexamethasone]—should now be considered second-line therapies. The primary focus should be on engaging the new targets, BCMA and GPRC5D.

References

1. Tecvayli + Talvey reduced the risk of disease progression or death by 89% and the risk of death by 62% in earlier-line relapsed/refractory multiple myeloma. News release. Johnson & Johnson. July 23, 2026. Accessed July 29, 2026. https://tinyurl.com/3ee86wxk
2. U.S. FDA approved Talvey (talquetamab-tgvs), a first-in-class bispecific therapy for the treatment of patients with heavily pretreated multiple myeloma. News release. The Janssen Pharmaceuticals. August 10, 2023. Accessed July 29, 2026. https://prn.to/3KwnjyD
3. Kumar S, Mateos MV, Ye JC, et al. Dual targeting of extramedullary myeloma with talquetamab and teclistamab. N Engl J Med. 2026;394(1):51-61. doi:10.1056/NEJMoa2514752